In recent years, drug-eluting implantable medical devices, such as, for example, stents, stent grafts, anastomosis devices, vascular grafts, vascular patches, AV shunts, catheters, guide wires, balloons, and filters, which contain one or more therapeutic drugs for local administration and controlled release of such therapeutic drugs, have gained more and more acceptance in the medical device industry. These implantable medical devices (or at least portions thereof) are typically formed of or coated by a biocompatible polymer that encapsulates or otherwise contains the therapeutic drug(s), which can be released into the surrounding environment from the implantable medical devices in a controlled and sustained manner.
The biocompatible polymer as described hereinabove can be made from a polymeric solution via various different processes, including, but not limited to: spray drying (for preparation of coatings), solvent casting or spin coating (for preparation of thin films or membranes), and spinning (for preparation of fibers). The polymeric solution typically contains one or more biocompatible homopolymers or copolymers (either biostable or biodegradable) and one or more therapeutic drugs dissolved in one or more solvents.
However, the solvent(s) used in the polymeric solution may have deleterious impact on living tissues. It is therefore important to remove the solvent(s) as completely as possible from the final polymeric composition, or at least reduce the solvent content in the final polymeric composition to a safe level defined by applicable government guidelines, while without reducing the amount of therapeutic drug(s) contained therein.
For example, the polymeric solution can be coated onto or cast into at least a portion of an implantable medical device to form a drug-containing thin polymeric film (e.g., about 3 to 6 mils), and the solvent(s) contained in the polymeric film can be gradually removed by evaporation under ambient conditions (i.e., room temperature and atmospheric pressure). The final solvent content in the polymeric film typically ranges from about 5 wt % to about 10 wt %, by total weight of the film. This solvent removal method under ambient conditions results in little or no reduction of the drug content in the polymeric film.
Alternatively, the solvent(s) contained in the polymeric film can be removed by low temperature drying, which is typically carried out at temperatures ranging from about 45° C. to about 60° C. under vacuum. The low temperature drying method can remove the solvent(s) with significant efficiency, resulting in a reduced final solvent content of from about 2 wt % to about 5 wt %, with little or not reduction of the drug content in the polymeric film.
Further, the solvent(s) can be removed by high temperature drying, which is typically carried out at temperatures ranging from about 60° C. to about 110° C. The high temperature drying method can further reduce of the final solvent content in the polymeric film. However, because the therapeutic drug(s) contained in the polymeric film is typically in an amorphous state and is therefore thermally unstable, the high temperature drying method may cause degradation of the therapeutic drug(s) and lead to significant reduction of the drug content in the polymeric film.
There is therefore a continuing need for improved methods for effectively removing solvent(s) from a drug-containing polymeric composition, without removing or degrading the therapeutic drug(s) contained therein.